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Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic

Nature Medicine volume 25, pages 547–553 (2019)Cite this article

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Abstract

Combination anti-retroviral therapy (ART) has revolutionized the treatment and prevention of HIV-1 infection. Taken daily, ART prevents and suppresses the infection. However, ART interruption almost invariably leads to rebound viremia in infected individuals due to a long-lived latent reservoir of integrated proviruses. Therefore, ART must be administered on a life-long basis. Here we review recent preclinical and clinical studies suggesting that immunotherapy may be an alternative or an adjuvant to ART because, in addition to preventing new infections, anti-HIV-1 antibodies clear the virus, directly kill infected cells and produce immune complexes that can enhance host immunity to the virus.

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Fig. 1: Approved monoclonal antibodies and bNAbs tested in clinical trials.
Fig. 2: bNAb characteristics and virus and host factors determine efficacy of passive immunotherapy for HIV-1 prevention and therapy.

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Acknowledgements

We thank members of the Klein and Nussenzweig laboratories for discussion. This work was supported by the NIH/National Institute of Allergy and Infectious Diseases Grant (U01AI129825), the Einstein-Rockefeller-CUNY Center for AIDS Research (1P30AI124414-01A1) and the BEAT-HIV Delaney grant UM1 AI126620 (M.C.); the Heisenberg-Program of the DFG (KL 2389/2-1), the European Research Council (ERC-StG639961) and the German Center for Infection Research (DZIF) (F.K.); the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1092074 and OPP1124068 and the NIH grants 1UM1 AI100663 and R01AI-129795 (M.C.N.); and the Robertson fund.

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Authors and Affiliations

  1. Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA

    Marina Caskey & Michel C. Nussenzweig

  2. Laboratory of Experimental Immunology, Institute of Virology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany

    Florian Klein

  3. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine, Cologne, Germany

    Florian Klein

  4. German Center for Infection Research, partner site Bonn–Cologne, Cologne, Germany

    Florian Klein

  5. Howard Hughes Medical Institute, Rockefeller University, New York, NY, USA

    Michel C. Nussenzweig

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Correspondence to Marina Caskey, Florian Klein or Michel C. Nussenzweig.

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There are patents on 3BNC117 and 10-1074, on which M.C.N is an inventor.

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Caskey, M., Klein, F. & Nussenzweig, M.C. Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic. Nat Med 25, 547–553 (2019). https://doi.org/10.1038/s41591-019-0412-8

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